Host Macrophage Response to Injectable Hydrogels Derived From ECM and α-Helical Peptides

Nazia Mehrban*, Catalina Pineda Molina, Lina M Quijano, James I Bowen, Scott A Johnson, Joseph Bartolacci, Jordan Chang, David J Scott, Dek N Woolfson, Martin Birchall, Stephen Badvlak

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Tissue engineering materials play a key role in how closely the complex architectural and functional characteristics of native healthy tissue can be replicated. Traditional natural and synthetic materials are superseded by bespoke materials that cross the boundary between these two categories. Here we present hydrogels that are derived from decellularised extracellular matrix and those that are synthesised from de novo α-helical peptides. We assess in vitro activation of murine macrophages to our hydrogels and whether these gels induce an M1-like or M2-like phenotype. This was followed by the in vivo immune macrophage response to hydrogels injected into rat partial-thickness abdominal wall defects. Over 28 days we observe an increase in mononuclear cell infiltration at the hydrogel-tissue interface without promoting a foreign body reaction and see no evidence of hydrogel encapsulation or formation of multinucleate giant cells. We also note an upregulation of myogenic differentiation markers and the expression of anti-inflammatory markers Arginase1, IL-10, and CD206, indicating pro-remodelling for all injected hydrogels. Furthermore, all hydrogels promote an anti-inflammatory environment after an initial spike in the pro-inflammatory phenotype. No difference between the injected site and the healthy tissue is seen after 28 days, indicating full integration. These materials offer great potential for future applications in regenerative medicine and towards unmet clinical needs.
Original languageEnglish
Pages (from-to)12
Number of pages141
JournalActa Biomaterialia
Volume111
Early online date21 May 2020
DOIs
Publication statusPublished - 15 Jul 2020

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

Keywords

  • synthetic biology
  • Hydrogels
  • Biomaterials
  • Peptide
  • ECM
  • Macrophage

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